This invention pertains to N-piperazineacetamide derivatives of 4,5-diphenyl-oxazoles, thiazoles and imidazoles having drug and bio-affecting properties and to their preparation and use. In particular the compounds of this invention are novel adenosine reuptake inhibitors that are neuroprotective under conditions of anoxia, ischemia or stroke.
Related art in terms of chemical structure may be represented by the following references.
Inoue, et al., in U.S. Pat. No. 4,101,660 disclosed and claimed a series of antiinflammatory and analgesic oxazole compounds (1) ##STR1## in which R.sup.1 is phenyl, R.sup.2 is hydrogen and R is hydroxyethyl. The series was extended to diphenyl derivatives (R.sup.1 =R.sup.2 =phenyl) in Chem. Abstr. 91:56986x and to piperidine derivatives (R=piperidinylalkyl) in Chem. Abstr. 91:56987y.
Various N-aryl-piperazinealkanamides of structure (2) ##STR2## have been reported as anti-ischemic agents for myocardial tissue and for treating sleep disorders.
N-aryl-4-(4,4-diarylbutyl)-1-piperazinealkanamides optionally substituted in the piperazine ring are described as coronary vasodilators, local anesthetics, CNS-stimulants and anticarrageenin agents in U.S. Pat. No. 3,267,104 to Hermans and Schaper.
A structurally related series of compounds with different X substituents attached to the piperazine ring was disclosed as being useful in treating ischemia in cardiac tissue in U.S. Pat. No. 4,776,125 to Van Daele.
A series of piperazine derivatives including compounds of structure (3) have been claimed in U.S. Pat. No. 4,948,796 to Hiraiwa et al., as being useful for the protection of cerebral cells from ischemia. ##STR3##
A method for treating neurodegenerative conditions by increasing extracellular concentrations of adenosine by use of, for example, adenosine transport inhibitors, was described by Marangos and Gruber in WO 91/04032.
There is nothing in any of the foregoing references, or in the general prior art, to suggest the novel antiischemic diphenyl-oxazoles, thiazoles and imidazoles of the present invention.